Darolutamide vs Proxalutamide - for a Hail Mary??

[JLS1]

Does anyone know the difference between darolutamide &. proxalutamide?

My husband is mCRPC. Diagnosed 3yrs ago and did the Casodex, then Docetaxel chemo, then RT to the L4-L1 followed by 1 round of Cabazitaxel + Carboplatin (for mets in liver). After that, went to Olaparib (Lynparza) took care of liver mets but not PSA, so added Zytiga, and that worked very well for over 1-1/2 years - until last summer. MO took him off the Lynparza, and switched the steroid from prednisone to dexamethasone to get more time on Zytiga.. He then started Xofigo, and after the 4th injection, suffered bone marrow failure, which we are dealing with now, via RBC infusions. MO said to stop Zytiga, as it is no longer helping. This leaves him 'only' on 2mg dexamethasone, Lupron shots (every 3 months) and Xgeva shots (monthly), and now, no surprise, a rapidly rising PSA (was 36 yesterday, and was 11.5 4 weeks ago). He desperately needs something asap, but the low blood counts exempt him from any other treatment and, so far, about every clinical trial I look at (except maybe ARV 110 - yet to be confirmed)

We just reran the Guardant test and no 'usable' markers stand out. MSI-High not detected. He has High AR Amplification, ARL702H 93.5% (which our MO says means Xtandi likely won't work), ART878A 0.6% and some "Variants of uncertain significance": ARM750T 2.2%, ARM750V 1.5%. ATME1612Q 0.2%. "Synonymous Alterations": ARL729L 0.6% I thought it was odd that Guardant suggests Bicalutamide (Casodex), which he took for a few months right after being diagnosed 3 years ago. Genetic tests, 3 years ago, of his tumor revealed somatic BRCA 2 and VHL (no idea what VHL is??) , and I remember some mention of PTEN (it's in our notes), but I think not enough to note on the report??

Proxalutamide sounded like it might be worth trying, if my husband could get in the trial, or get the drug via "Right to Try".....then our MO said it's similar to Darolutamide, which may be possible to get. We were on a list with Dr. Tagawa's group at Weill Cornell for AC225, but with low blood counts, that's off the table for now (unless blood counts can recover enough).. I wonder if the cholera vaccine might be worth trying, and safe....

[Tall_Allen]

I hope proxalutamide works for him. It is thought to downregulate the AR, which might slow things down.

[JLS1 in reply to Tall_Allen]

We were trying to get that, but now it appears it may be a lot easier to get the darolutamide. Do you know how that compares to proxalutamide, if it works as well?

[Tall_Allen in reply to JLS1]

There is no comparative data.

[JLS1 in reply to Tall_Allen]

This afternoon I talked to an oncologist running one of the proxalutamiode clinical trials. He's very excited about it, says it's helping 80% of his patients, and he feels it will be approved pretty quickly for mCRPC. -says it works better vs. Xtandi, with a one-two punch. Unfortunately the ONLY reason my husband can't get into this trial is because he had one round of cabazataxel + carboplation chemo. The trial will only accept patients who had one type of chemo. My husband's low blood counts wouldn't exclude him! He couldn't say what the difference is between proxalutamide and daralutamide.

Still waiting to hear more about Arvinas' ARV-110 trial, out of Yale. Phase 1, but it sounds pretty safe:

clinicaltrialsarena.com/new...

/"Arvinas CEO John Houston said: “We are seeing a favourable overall safety profile for both clinical programs to date, and dose-proportional exposures of ARV-110."

[Tall_Allen in reply to JLS1]

Did the PI tell you specifically that the chemo cocktail excludes you? When they say "one line" of chemo, that usually means one course, whether it was docetaxel, cabazitaxel, or either with carboplatin. Ask for a ruling from the Study Director:Phoebe Zhang of Suzhou Kintor Pharmaceuticals,.

[JLS1 in reply to Tall_Allen]

Thank you SO much!!

Our MO was able to get the Darolutamide approved by our insurance, so given we now have that in hand, we'll try it. He said it's very similar to Proxalutamide. Fingers crossed it works as well! We'll find out in a few weeks and I'll report here.

Also, my husband recently added melatonin. Hopefully it will be synergistic with the Darolutamide

I will still follow up with the Proxalutamide and other Plan Bs, just in case. Can't waste any time here!!